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The immunogenicity of tendon-derived stem cells (TDSCs) has implications for their clinical use for the promotion of tendon repair. The immunogenicity and escape mechanisms of rat patellar TDSCs were examined after allogeneic transplantation. Our results showed that TDSCs exhibited low immunogenicity as evidenced by the following: (i) the incubation of target TDSCs with immunized serum did not show antibody recognition and did not induce the complement-dependent cytotoxicity; (ii) target TDSCs elicited a very low level of lymphocyte proliferation and did not exhibit host lymphocyte-mediated cytotoxicity; and (iii) target TDSCs dose dependently suppressed the phorbol 12-myristate 13-acetate (PMA)- and ionomycin-induced host lymphocyte proliferation. For the mechanistic studies, TDSCs expressed major histocompatibility complex (MHC)-I but a very low level of MHC-II, CD86 and CD80 for the induction of T-cell response. Also, TDSCs were found to express intracellular Fas and FasL. γ-IFN pretreatment did not increase the level of MHC-II and CD86 for the upregulation of immune response. Moreover, the immunosuppressive mediators indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta 1 (TGF-β1) were found not to be involved in the escape mechanism of target TDSCs from host lymphocyte attack. In conclusion, allogeneic TDSCs exhibited low immunogenicity. Allogeneic TDSCs might be used for transplantation.

Purpose: This study proposes treatment methods to provide a mechanically competent, immunocompatible, and sterile porcine graft for human knee ligament reconstruction., Methods: The anterior cruciate ligament (ACL) was reconstructed by using treated porcine patellar tendon grafts or controls of untreated porcine grafts or allografts in 20 rhesus monkeys. Animals were stratified into 2-, 6-, and 12-month postreconstruction cohorts. Serologic and histologic assessments were performed to evaluate host immunological and cellular response. Healing and functional integrity of the ACL reconstructions were assessed by tensile biomechanical testing., Results: Untreated porcine grafts were acutely resorbed and rejected, whereas treated porcine grafts and allografts were incorporated by the host as functional grafts. Temporal histologic assessment of treated porcine grafts and rhesus grafts revealed gradual host cellular infiltration and graft collagen remodeling through a similar mechanism of ligamentization. Biomechanical evaluations support graft functional integration with no difference between allograft and treated graft reconstructions., Conclusion: Rhesus allograft and treated porcine grafts presented with similar healing profiles in a long-term evaluation of ACL reconstruction., Clinical Relevance: Immunochemical modification and sterilization of porcine patellar tendon grafts may improve initial biocompatibility and long-term functionality of xenografts in musculoskeletal applications.